Acanthosis nigricans (AN) is a diffuse, velvety thickening and hyperpigmentation of the skin, chiefly in axillae and other body folds, which may be related to hereditary factors, associated endocrine disorders, obesity, drug administration, and, in one rare form, malignancy.
Type 1—Hereditary Benign AN: No associated endocrine disorder.
Type 2—Benign AN: Associated with insulin resistance (IR), impaired glucose tolerance, IR diabetes mellitus (DM), hyperandrogenism, acromegaly, gigantism, Cushing’s disease, growth hormone, hypogonadism, Addison’s disease, hypothyroidism, polycystic ovary syndrome, or total lipodystrophy.
Type 3—Pseudo-AN: Obesity-induced IR, darker skin types.
Type 4—Drug-induced AN: Nicotinic acid, oral contraceptives, insulin, or other exogenous hormone treatments.
Type 5—Malignant AN Paraneoplastic, usually adenocarcinoma; less commonly, lymphoma.
AGE Any age. Peak: puberty to adulthood.
GENDER M = F.
INCIDENCE Up to 19% of the population. Incidence thought to be rising with increased obesity and diabetes in both pediatric and adult populations.
RACE African Americans > Hispanics, Native Americans > Caucasians, Asians.
Epidermal changes of AN are likely caused by triggers that stimulate keratinocyte and fibroblast proliferation. In benign AN, the trigger is likely insulin or an insulin-like growth factor. In malignant AN, the trigger is likely the tumor or tumor secretions. Growth receptors that have been implicated in the development of AN include fibroblast growth factor receptor (FGFR), insulin-like growth factor receptor-1 (IGFR1), and epidermal growth factor receptor (EGFR).
AN has an asymptomatic, insidious onset. The first visible change is darkening of pigmentation which gradually progresses to velvety plaques that may be pruritic.
TYPE Plaque.
COLOR Dark brown to black, hyperpigmented, skin appears dirty. Longstanding lesions may show hyperlinearity of skin markings.
PALPATION Velvety, rugose, mammillated.
DISTRIBUTION Posterior neck > axillae (Fig. 18-1), groin > antecubital, knuckles, submammary, umbilicus, areola. Usually symmetric.
MUCOUS MEMBRANES Oral, nasal, laryngeal, and esophagus: velvety texture with delicate furrows.
NAILS Leukonychia, hyperkeratosis.
OTHER Skin tags in same areas, likely due to similar growth-factor stimulation.
OCULAR Papillomatous lesions on the eyelids and conjunctiva.
BENIGN AN Obesity or underlying endocrine disorder.
MALIGNANT AN Underlying malignancy most commonly gastric adenocarcinoma (70%).
AN can be confused with confluent and reticulated papillomatosis of Gougerot and Carteaud (CARP), terra firma-forme dermatosis, hypertrichosis, Becker’s nevus, epidermal nevus, hemochromatosis, Addison’s disease, or pellagra.
DERMATOPATHOLOGY Papillomatosis, hyperkeratosis; epidermis thrown into irregular folds, showing varying degrees of acanthosis.
Type 1: Accentuated at puberty, and, at times, regresses when older.
Type 2: Prognosis related to severity of IR. AN may regress subsequent to treatment of the IR state.
Type 3: AN may regress subsequent to significant weight loss.
Type 4: Resolves when causative drug is discontinued.
Type 5: Poor prognosis, since the underlying malignancy is often aggressive. Adults with new-onset AN have an average survival time of 2 years.
Treatment of AN should include a careful workup to exclude any underlying endocrine disorder. In children, AN is very rarely a sign of an underlying malignancy. Correction of any underlying disorder (obesity, endocrine disease) improves the skin condition. Cosmetically, AN is difficult to treat, but some improvement may be gained with topical keratolytics (retinoic acid, salicylic acid, or urea) or topical vitamin D analogs (calcipotriene). In severe cases, systemic retinoids (acitretin, isotretinoin), metformin, dietary fish oil, dermabrasion, and laser therapy have reported successes. In adults, malignant AN may respond to cyproheptadine because it may inhibit the release of tumor products.
Necrobiosis lipoidica (NL) is a cutaneous disorder characterized by distinctive, sharply circumscribed, red–brown plaques with palpable rims and yellow–brown atrophic centers occurring on the lower legs. It is frequently associated with DM.
SYNONYM Necrobiosis lipoidica diabeticorum (NLD).
AGE Any age, peak: 25 to 30 years. Seen earlier in juvenile diabetic patients.
GENDER F > M, 3:1.
INCIDENCE <1% of patients with diabetes.
ETIOLOGY 65% patients with diabetes. Predilection for posttraumatic sites.
NL is a granulomatous inflammatory reaction caused by alterations in collagen. The exact cause is unknown, but in DM, NL is thought to be secondary to diabetic microangiopathy. In non-DM cases, the trigger may be posttraumatic, postinflammatory, metabolic, or vasculitic antibody-mediated. A possible association with underlying inflammatory thyroid disease has also been suggested.
NL skin lesions evolve slowly and enlarge over months to years. The skin lesions are typically asymptomatic, but ulcerated lesions are painful. Diabetes may or may not be present at the time of onset of lesions and is present in up to 65% of NL patients.
TYPE Papules, plaques, ulcers.
SIZE 1 to 3 mm up to several centimeters.
COLOR Brownish-red border; yellow atrophic shiny center (Fig. 18-2).
SHAPE Serpiginous, annular, irregularly irregular.
ARRANGEMENT Often symmetrical.
DISTRIBUTION DISTAL Legs and feet (80%) > arms, trunk, face, and scalp.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
